SI9400195B - Antagonisti endotelinskih receptorjev - Google Patents
Antagonisti endotelinskih receptorjev Download PDFInfo
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- SI9400195B SI9400195B SI9400195A SI9400195A SI9400195B SI 9400195 B SI9400195 B SI 9400195B SI 9400195 A SI9400195 A SI 9400195A SI 9400195 A SI9400195 A SI 9400195A SI 9400195 B SI9400195 B SI 9400195B
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- hydrogen
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- 229940118365 Endothelin receptor antagonist Drugs 0.000 title abstract 2
- 239000002308 endothelin receptor antagonist Substances 0.000 title abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 35
- 239000001257 hydrogen Substances 0.000 claims 34
- 150000002431 hydrogen Chemical class 0.000 claims 22
- 125000000217 alkyl group Chemical group 0.000 claims 21
- 150000001875 compounds Chemical class 0.000 claims 15
- 229910052736 halogen Inorganic materials 0.000 claims 13
- 150000002367 halogens Chemical class 0.000 claims 13
- 125000003545 alkoxy group Chemical group 0.000 claims 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 10
- 229910052794 bromium Inorganic materials 0.000 claims 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 7
- 229910052731 fluorine Inorganic materials 0.000 claims 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 229910052799 carbon Inorganic materials 0.000 claims 5
- 125000003342 alkenyl group Chemical group 0.000 claims 4
- -1 benzodioxanyl Chemical group 0.000 claims 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 3
- 125000000304 alkynyl group Chemical group 0.000 claims 3
- 125000001041 indolyl group Chemical group 0.000 claims 3
- 150000003536 tetrazoles Chemical class 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- 125000000160 oxazolidinyl group Chemical group 0.000 claims 2
- 125000002971 oxazolyl group Chemical group 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 239000001301 oxygen Substances 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- 125000001984 thiazolidinyl group Chemical group 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 1
- QUKHCYJPMHKWKW-UHFFFAOYSA-N 1,3-diphenyl-1h-indene-2-carbonitrile Chemical compound N#CC1=C(C=2C=CC=CC=2)C2=CC=CC=C2C1C1=CC=CC=C1 QUKHCYJPMHKWKW-UHFFFAOYSA-N 0.000 claims 1
- QWCRGCBOYCCWTN-UHFFFAOYSA-N 1,3-diphenyl-1h-indene-2-carboxylic acid Chemical compound OC(=O)C1=C(C=2C=CC=CC=2)C2=CC=CC=C2C1C1=CC=CC=C1 QWCRGCBOYCCWTN-UHFFFAOYSA-N 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 claims 1
- 102000010180 Endothelin receptor Human genes 0.000 claims 1
- 108050001739 Endothelin receptor Proteins 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 208000001647 Renal Insufficiency Diseases 0.000 claims 1
- 230000008485 antagonism Effects 0.000 claims 1
- 208000026106 cerebrovascular disease Diseases 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- GLCKXJLCYIJMRB-UPRLRBBYSA-N enrasentan Chemical compound C1([C@H]2[C@@H]([C@H](C3=CC=C(C=C32)OCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1OCCO GLCKXJLCYIJMRB-UPRLRBBYSA-N 0.000 claims 1
- GRJRDNBITVZQRX-UHFFFAOYSA-N ethyl 1,3-diphenyl-1h-indene-2-carboxylate Chemical compound CCOC(=O)C1=C(C=2C=CC=CC=2)C2=CC=CC=C2C1C1=CC=CC=C1 GRJRDNBITVZQRX-UHFFFAOYSA-N 0.000 claims 1
- GTIMVTFVLMOUFJ-UHFFFAOYSA-N ethyl 3-hydroxy-1,3-diphenyl-1,2-dihydroindene-2-carboxylate Chemical compound CCOC(=O)C1C(C=2C=CC=CC=2)C2=CC=CC=C2C1(O)C1=CC=CC=C1 GTIMVTFVLMOUFJ-UHFFFAOYSA-N 0.000 claims 1
- 201000006370 kidney failure Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 150000002901 organomagnesium compounds Chemical class 0.000 claims 1
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 abstract 2
- 125000003454 indenyl group Chemical class C1(C=CC2=CC=CC=C12)* 0.000 abstract 1
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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Claims (9)
1 Patentni zahtevki 1. Spojina s formulo (I)
kjer je Rj -X(CH2)nAr ali -X(CH2)nR8 ali R,
R2 vodik, Ar, C!_4alkil ali (c); P, -X(CH2)nR8; P2 -X(CH2)nR8 ali -X-R9-Y; R3 in R5 sta neodvisno vodik, Rn, OH, C!.8 alkoksi, S(0)qR„, N(R<,)2, Br, F, J, Cl, CF3, NHCOR«, RuC02R7, -X-R9-Y ali -X(CH2)nR8, kjer je lahko vsaka metilenska skupina v -X(CH2)nR8 nesubstituirana ali substituirana z eno ali dvema -(CH2)nAr skupinama; R4 je vodik, Rn, OH, alkoksi, S(0)qRn, N(R^)2, -X(Rn), Br, F, J, Cl ali NHCOR<5, kjer je lahko C 1.5 alkoksi, nesubstituiran ali substituiran z OH, metoksi ali halogenom; R^ je neodvisno vodik ali Ci_4alkil; R7 je neodvisno vodik, Ci_i0alkil, C24oalkenil ali C2.8alkinil, od katerih so lahko vsi nesubstituirani ali substituirani z enim ali več OH, N(R$)2, C02R}2, halogenom ali XCi_5alkilom ali je R7 (CH2)nAr; 2 R8 je vodik, Rn, C02R7, C02C(Rn)2 0(CO)XR7, P03(R7)2, S02NR7R„, NR7S02Rh, C0NR7S02Rn, S03R7, S02R7, P(0)(OR7)R7, CN, C(0)N(R6)2, -C02(CH2)mC(0)N(R6)2, C(R„)2N(R7)2, tetrazol ali OR,; R9 je (CH2)n, dvovalentni Ci.]0alkil, dvovalentni C2_i0alkenil ali fenil, od katerih so lahko vsi nesubstituirani ali substituirani z enim ali več OH, N(R,)2, COOH, halogenom, ali je R9 lahko >C=0 ali XCi_5alkil; Rio je R3 ali R4; Rn je vodik, Ar, Ci.galkil, C2.8alkenil, C2.8alkinil, od katerih so lahko vsi nesubstituirani ali substituirani z enim ali več OH, CH2OH, N(R6)2 ali halogenom; pod pogojem, da kadar je Rn prisoten v skupini RnC02R7, Rn ni vodik; Rj2 je vodik, Ci_6alkil, C2.6alkenil ali C2.7alkinil; X je (CH2)n, O, NR, ali S(0)q; Y je CH3 ali X(CH2)nAr; Arje
(a) (b) naftil, indolil, piridil, tienil, oksazolidinil, oksazolil, tiazolil, izotiazolil, pirazolil, triazolil, tetrazolil, imidazolil, imidazolidinil, tiazolidinil, izoksazolil, oksadiazolil, tiadiazolil, morfolinil, piperidinil, piperazinil, pirolil ali pirimidil; od katerih so lahko vsi nesubstituirani ali substituirani z eno ali več skupinami R3 ali R4; A je C=0 ali [C(R,)2]m; B je -CH2- ali -0- Zi in Z2 sta neodvisno vodik, Ci_8alkil, C2.8alkenil, C2.8alkinil, OH, Ci_8alkoksi, S(0)qCi_8alkil, N(R,)2, Br, F, J, Cl, NHCOR,, -X-R9-Y, -X(CH2)nR8, fenil, benzil ali C3_6cikloalkil in je lahko Ci_8alkil, C2.8alkenil ali C2.8alkinil v danem primeru 3 substituiran s COOH, OH, CO(CH2)nCH3, CO(CH2)nCH2N(R6)2 ali halogenom; ali sta Zj in Z2 skupaj lahko -O-A-O- na sosednjih ogljikih; Z3 je Zi ali -X-R9-Y; Q je 0, 1 ali 2; nje celo število od 0 do 6; m je 1, 2 ali 3; in črtkana črta kaže na fakultativno prisotnost dvojne vezi; ali njihovo farmacevtsko sprejemljivo sol; pod pogojem, da r2 ni vodik, kadar je X S(0)q; Ri in R7 nista vodik, kadar je Q 1 ali 2 v S(0)qRn ali S(0)qR7; kadar je prisotna fakultativna dvojna vez v formuli (I), je lahko le en R10 in ni nobenega Pi ter P2 ni NR^RgV; kadar je prisotna fakultativna dvojna vez v formuli (I) in je X-R2 vezan na dvojno vez, Xni NR^; kadar je prisotna fakultativna dvojna vez in je Ri vezan direktno na dvojno vez, Ri ni NR^Ar; kadar je R3, R5, Zb Z2 ali Z3 X(CH2)nR8 in n ni 0, je X kisik ali NR$, kadar je R8 ORč ali C02H; kadar je R« C02C(Rn)20(CO)XR7, X ni S(0)q; spojina s formulo I ni metil, l,3-difenilinden-2-karboksilat; etil l,3-difenilinden-2-karboksilat; l,3-difenil-2-cianoinden; ali etil l,3-difenil-3-hidroksiindan-2-karboksilat; in nadalje pod pogojem, da so izključene spojine, kjer je R, -X(CH2)nAr ali -X(CH2)nR8 ali
(CH2)m (c) 4 R2 vodik, Ar ali (c); P! -X(CH2)nR8; P2 -X(CH2)nR8 ali -XR9Y; R3 in R5 sta neodvisno vodik, Rn, OH, C].8alkoksi, S(0)qRn, N(R^)2, Br, F, J, Cl, CF3, NHCOR*, -XR9-Y ali -X(CH2)nR8, kjer so lahko metilenske skupine, -X(CH2)nR8 nesubstituirane ali substituirane z eno ali več -(CH2)nAr skupinami; R4 je vodik, Rn, OH, Ci_5alkoksi, S(0)qRn, N(R^)2, -X(Rn), Br, F, J, Cl ali NHCOR^, kjer je lahko C].5alkoksi nesubstituiran ali substituiran z OH, metoksi ali halogenom; Rč je neodvisno vodik ali Ci_4alkil; R7 je neodvisno vodik, Ci_6alkil ali (CH2)nAr; Rs je vodik, Rn, C02H, P03H2, P(0)(0H)R7 ali tetrazol; R9 je Cmoalkil, C2.10alkenil ali fenil, od katerih so lahko vsi nesubstituirani ali substituirani z enim ali več OH, N(R^)2, COOH, halogenom ali XCi_5alkilom; R10 je R3 ali R4; R„ je Ci.galkil, C2.8alkenil, C2.8alkinil, od katerih so prav tako vsi lahko nesubstituirani ali substituirani z enim ali več OH, CH2OH, N(R^)2 ali halogenom; X je (CH2)n, O, NR^ ali S(0)q; Y je CH3 ali -CH2X(CH2)nAr; Arje:
(b) naftil, indolil, piridil ali tienil, oksazolidinil, oksazolil, tiazolil, izotiazolil, pirazolil, triazolil, tetrazolil, imidazolil, imidazolidinil, tiazolidinil, izoksazolil, oksadiazolil, tiadiazolil, morfolinil, piperidinil, piperazinil, pirolil ali pirimidil; od katerih so lahko vsi nesubstituirani z eno ali več R3 ali R4 skupinami; 5 A je C=0 ali [CCR^U; B je -CH2- ali -O-; Z\ in Z2 sta neodvisno vodik, Ci.8alkil, C2_8alkenil, C2.galkinil, OH, Ci_8alkoksi, S(0)qCi_8alkil, N(R<5)2, Br, F, J, Cl, NHCORe, -X(CH2)nR8, fenil, benzil ali C3.6cikloalkil, kjer so lahko Ci.8alkil, C2.8alkenil ali C2.8alkinil v danem primeru substituirani s COOH, OH, CO(CH2)nCH3, CO(CH2)nCH2N(R6)2 ali halogenom; ali sta Z\ in Z2 skupaj lahko -O-A-O- na sosednjih ogljikih; Z3 je Z\ ali XR9Y; q je 0, 1 ali 2; nje celo število od 0 do 6; m je 1, 2 ali 3.
2. Spojina po zahtevku 1, označena s tem, daje Ri X(CH2)nAr, dihidrobenzofuranil, benzodioksanil, cikloheksil Ci_4alkil; R2 je del s formulo (a) ali (b), C^aHdl, indolil ali vodik; R3 in R5 sta neodvisno vodik, OH, Ci_5alkoksi, halogen, -OCj^alkilfenil, R„C02R7, C,.4alkil, N(R6)2, NH(CO)CH3, -X(CH2)nR8, -X-R9-Y, piridil, fenil ali S(0)qC,.5alkil; R4 je vodik, OH, C,.5alkoksi, halogen, CMalkil, Ν(^)2, NH(CO)CH3 ali S(0)qCi_5alkil; Z\, Z2 in Z3 so neodvisno X-R9-Y, benzil, vodik, OH, Ci_5alkoksi, -N(R$)2, S(0)qCj_8alkil, NHCOR^, X(CH2)nR8 ali halogen, ali sta lahko Z\ in Z2 skupaj -O-A-O na sosednjih ogljikih; Ρ] in P2 sta neodvisno vodik, C02H ali tetrazol; Arje del s formulo (a) ali (b), fenil ali piridil in je X (CH2)n ali kisik.
3. Spojina po zahtevku 2, označena s tem, daje R3 vodik, -X(CH2)nR8 ali RnC02R7; R4 in R5 sta neodvisno vodik, OH, C^alkoksi, SCi„5alkil, F, Br, C1.3alkil ali NH2; sta Zi in Z3 vodik in je Z2 vodik, OH, C^alkoksi, halogen, X(CH2)nR8, NH2, benzil ali NH(CO)CH3, ali sta lahko Z\ in Z2 skupaj O-A-O na sosednjih ogljikih. 6
4. Spojina po zahtevku 3, označena s tem, da je Rt del s formulo (b) in R2 del s formulo (a) ali (b); A je CH2, B je -0-; ni fakultativne dvojne vezi; R! in XR2 sta trans glede na Pi; Z2 je OH, C^alkoksi, -OCH2CHCH3 ali vodik, Zi je vodik; R3 je vodik, XAr, X(CH2)qC02H, X(CH2)qC0NR7S02Rn ali CH=CHC02H, R4 je vodik ali Ci_2alkoksi; in so R5, Ri0 in P2 vodik.
5. Spojina, označena s tem, dajo izberemo iz skupine, v kateri so: (+)(1 S, 2R, 3 S)-3-(2-karboksimetoksi-4-metoksifenil)-1 -(3,4-metilendioksifenil)-5-(prop-l-iloksi)indan-2-karboksilna kislina in dinatrijeva sol (+)(1S, 2R, 3S)-3-[2-(2-hidroksiet-l-iloksi)-4-metoksifenil)-1-(3,4-metilendioksifenil)-5-(prop-1 -iloksi)indan-2-karboksilne kisline; dinatrijev (1RS, 2RS, 3SR)-3-[2-[4-karboksipiridin-3-il)oksi)-4-metoksifenil)-l-(3,4-metilendioksifenil)-5-(prop-1 -iloksi)indan-2-karboksilat.
6. Farmacevtski sestavek, označen s tem, da vsebuje spojino po zahtevku 1 ali zahtevku 5 ter farmacevtsko sprejemljiv nosilec.
7. Uporaba spojine po kateremkoli od zahtevkov 1 do 5 ali njene farmacevtsko sprejemljive soli za pripravo zdravila za zdravljenje stanja, ki zahteva antagoniziranje endotelinskih receptorjev.
8. Uporaba spojine po kateremkoli od zahtevkov 1 do 5 ali njene farmacevtsko sprejemljive soli za pripravo zdravila za zdravljenje hipertenzije, odpovedi ledvic ali cerebrovaskulame bolezni. 7
9. Postopek za pripravo spojine s formulo (I) po zahtevku 1 ali zahtevku 5, ali njene farmacevtsko sprejemljive soli, označen s tem, da spojino s formulo (II) 7
kjer so Z]? Z2, Z3 in Ri, kot je opisano v zahtevku 1, ali skupina, ki je vanje pretvorljiva, X pa je Ci-5-alkil, presnovimo z organomagnezijevo spojino s formulo (III) R2-(CH2)n-MgBr (III) kjer je R2, kot je opisano v zahtevku 1, ali skupina, ki je vanj pretvorljiva, v primernem topilu, da dobimo spojino s formulo (IV)
(IV) ki jo reduciramo in nato, po želji ali po potrebi a) vstavimo Ri0 (kadar je različen od vodika) s konjugirano adicijo; in/ali b) alkiliramo ali aciliramo, da dobimo spojine, kjer sta P! in P2 različna od C02H; in/ali c) pretvorimo Rj, R2, Zls Z2 in Z3; da dobimo spojino s formulo (I).
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| US6681893A | 1993-04-27 | 1993-04-27 |
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| WO1995033748A1 (en) * | 1994-06-09 | 1995-12-14 | Smithkline Beecham Corporation | Endothelin receptor antagonists |
| JPH10501812A (ja) * | 1994-06-20 | 1998-02-17 | スミスクライン・ビーチャム・コーポレイション | エンドセリン受容体拮抗薬 |
| JPH10512855A (ja) * | 1994-12-23 | 1998-12-08 | スミスクライン・ビーチャム・コーポレイション | 化合物および方法 |
| ZA969363B (en) | 1995-11-08 | 1997-11-18 | Smithkline Beecham Corp | An improved process for preparing aromatic ring-fused cyclopentane derivatives. |
| US6080862A (en) * | 1995-11-08 | 2000-06-27 | Smithkline Beecham Corporation | Stereoselective synthesis of endothelin receptor antagonists |
| CA2236924A1 (en) * | 1995-11-08 | 1997-05-15 | Smithkline Beecham Corporation | Stereoselective synthesis of endothelin receptor antagonists |
| US6162932A (en) * | 1995-11-08 | 2000-12-19 | Smithkline Beecham Corporation | Stereoselective synthesis of endothelin receptor antagonists |
| US5977117A (en) * | 1996-01-05 | 1999-11-02 | Texas Biotechnology Corporation | Substituted phenyl compounds and derivatives thereof that modulate the activity of endothelin |
| US5932553A (en) | 1996-07-18 | 1999-08-03 | The Regents Of The University Of California | Illudin analogs useful as antitumor agents |
| US5723632A (en) * | 1996-08-08 | 1998-03-03 | Mgi Pharma, Inc. | Total synthesis of antitumor acylfulvenes |
| JP3076066B2 (ja) | 1996-08-27 | 2000-08-14 | 塩野義製薬株式会社 | クロメン−３−カルボン酸誘導体 |
| US5929106A (en) * | 1997-10-27 | 1999-07-27 | Smithkline Beecham Corporation | Endothelin receptor antagonists |
| US6025328A (en) | 1998-02-20 | 2000-02-15 | The Regents Of The University Of California | Antitumor agents |
| US7141603B2 (en) | 1999-02-19 | 2006-11-28 | The Regents Of The University California | Antitumor agents |
| US6410554B1 (en) | 1998-03-23 | 2002-06-25 | Merck & Co., Inc. | Combination therapy for the treatment of benign prostatic hyperplasia |
| EP1070041B1 (en) * | 1998-04-09 | 2003-07-02 | Merck & Co., Inc. (a New Jersey corp.) | Phosphate-mediated cyclization |
| AR022230A1 (es) | 1999-01-12 | 2002-09-04 | Abbott Gmbh & Co Kg | Compuestos de triazol, composicion farmaceutica que los comprende y uso de los mismos para preparar dicha composicion |
| US8168616B1 (en) | 2000-11-17 | 2012-05-01 | Novartis Ag | Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension |
| GB0327839D0 (en) | 2003-12-01 | 2003-12-31 | Novartis Ag | Organic compounds |
| CA2558020A1 (en) | 2004-03-17 | 2005-09-29 | Novartis Ag | Use of renin inhibitors in therapy |
| US7423176B2 (en) | 2004-04-13 | 2008-09-09 | Cephalon, Inc. | Bicyclic aromatic sulfinyl derivatives |
| EP1831152B1 (en) | 2004-12-21 | 2008-09-24 | F. Hoffmann-La Roche AG | Tetralin and indane derivatives and uses thereof as 5-ht antagonists |
| WO2006137222A1 (ja) * | 2005-06-24 | 2006-12-28 | Tokyo Medical And Dental University | 薬剤溶出速度制御方法、及び薬剤溶出性ステント被膜用組成物 |
| WO2007019308A2 (en) | 2005-08-03 | 2007-02-15 | The Regents Of The University Of California | Illudin analogs useful as anticancer agents |
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